Talk abstracts
Talk on Friday 03:45-04:00pm submitted by Monica Mannings
Pnrc2-dependent mRNA decay and translational control mechanisms promote oscillatory gene expression during vertebrate segmentation
Monica Mannings (The Ohio State University Molecular Genetics Department), Thomas Gallagher (The Ohio State University Molecular Genetics Department), Kiel Tietz (The Ohio State University Molecular Genetics Department), Sharon Amacher (The Ohio State University Molecular Genetics Department)
Abstract:
During early vertebrate embryogenesis, muscle and skeletal precursors are sequentially grouped into reiterated segments, called somites, in a process called somitogenesis. Sequential somite formation is established by a genetic oscillator called the segmentation clock, comprised of a network of genes called cyclic genes or segmentation clock genes, that are reiteratively expressed in the unsegmented mesoderm with defined periodicity. Precise regulation of mRNA production, translation, and decay drive the pace and amplitude of segmentation clock oscillations and our work explores post-transcriptional mechanisms that regulate oscillatory expression. Previous work in the Amacher lab showed that Proline-rich nuclear receptor coactivator 2 (Pnrc2) promotes cyclic gene mRNA decay in zebrafish embryos and that loss of pnrc2 results in accumulation of cyclic gene mRNAs. Despite increased levels of cyclic gene mRNAs, pnrc2 mutants display normal protein oscillations and segment boundary formation. Using polysome profiling to probe the translation status of cyclic gene mRNAs in pnrc2 mutant embryos, we show here that the accumulated cyclic gene mRNAs her1, her7, dlc, and rhov are disengaged from translational machinery. Cyclic gene mRNA 3’UTR analysis identified two cis-regulatory elements within the 3’UTRs of her1 and dlc, a Pumilio Response Element (PRE) and AU-rich Element (ARE), that promote reporter transcript decay. Both Pumilio and ARE-binding proteins are well-known regulators of mRNA decay and translation. We are investigating their role in regulating cyclic gene mRNA stability and translation, in wild-type and pnrc2 mutant backgrounds, to understand mechanistically how vertebrate patterning is robustly maintained using multiple layers of post-transcriptional regulation.
Keywords: decay, translation, oscillations